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Bone & Joint Research
Vol. 13, Issue 4 | Pages 157 - 168
4 Apr 2024
Lin M Chen G Yu H Hsu P Lee C Cheng C Wu S Pan B Su B

Aims

Osteosarcoma is the most common primary bone malignancy among children and adolescents. We investigated whether benzamil, an amiloride analogue and sodium-calcium exchange blocker, may exhibit therapeutic potential for osteosarcoma in vitro.

Methods

MG63 and U2OS cells were treated with benzamil for 24 hours. Cell viability was evaluated with the MTS/PMS assay, colony formation assay, and flow cytometry (forward/side scatter). Chromosome condensation, the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay, cleavage of poly-ADP ribose polymerase (PARP) and caspase-7, and FITC annexin V/PI double staining were monitored as indicators of apoptosis. Intracellular calcium was detected by flow cytometry with Fluo-4 AM. The phosphorylation and activation of focal adhesion kinase (FAK) and signal transducer and activator of transcription 3 (STAT3) were measured by western blot. The expression levels of X-linked inhibitor of apoptosis protein (XIAP), B-cell lymphoma 2 (Bcl-2), B-cell lymphoma-extra large (Bcl-xL), SOD1, and SOD2 were also assessed by western blot. Mitochondrial status was assessed with tetramethylrhodamine, ethyl ester (TMRE), and intracellular adenosine triphosphate (ATP) was measured with BioTracker ATP-Red Live Cell Dye. Total cellular integrin levels were evaluated by western blot, and the expression of cell surface integrins was assessed using fluorescent-labelled antibodies and flow cytometry.


Bone & Joint Open
Vol. 4, Issue 6 | Pages 424 - 431
5 Jun 2023
Christ AB Piple AS Gettleman BS Duong A Chen M Wang JC Heckmann ND Menendez L

Aims

The modern prevalence of primary tumours causing metastatic bone disease is ill-defined in the oncological literature. Therefore, the purpose of this study is to identify the prevalence of primary tumours in the setting of metastatic bone disease, as well as reported rates of pathological fracture, postoperative complications, 90-day mortality, and 360-day mortality for each primary tumour subtype.

Methods

The Premier Healthcare Database was queried to identify all patients who were diagnosed with metastatic bone disease from January 2015 to December 2020. The prevalence of all primary tumour subtypes was tabulated. Rates of long bone pathological fracture, 90-day mortality, and 360-day mortality following surgical treatment of pathological fracture were assessed for each primary tumour subtype. Patient characteristics and postoperative outcomes were analyzed based upon whether patients had impending fractures treated prophylactically versus treated completed fractures.


The Bone & Joint Journal
Vol. 105-B, Issue 10 | Pages 1115 - 1122
1 Oct 2023
Archer JE Chauhan GS Dewan V Osman K Thomson C Nandra RS Ashford RU Cool P Stevenson J

Aims

Most patients with advanced malignancy suffer bone metastases, which pose a significant challenge to orthopaedic services and burden to the health economy. This study aimed to assess adherence to the British Orthopaedic Oncology Society (BOOS)/British Orthopaedic Association (BOA) guidelines on patients with metastatic bone disease (MBD) in the UK.

Methods

A prospective, multicentre, national collaborative audit was designed and delivered by a trainee-led collaborative group. Data were collected over three months (1 April 2021 to 30 June 2021) for all patients presenting with MBD. A data collection tool allowed investigators at each hospital to compare practice against guidelines. Data were collated and analyzed centrally to quantify compliance from 84 hospitals in the UK for a total of 1,137 patients who were eligible for inclusion.


Bone & Joint Research
Vol. 13, Issue 12 | Pages 725 - 740
5 Dec 2024
Xing J Liu S

Addressing bone defects is a complex medical challenge that involves dealing with various skeletal conditions, including fractures, osteoporosis (OP), bone tumours, and bone infection defects. Despite the availability of multiple conventional treatments for these skeletal conditions, numerous limitations and unresolved issues persist. As a solution, advancements in biomedical materials have recently resulted in novel therapeutic concepts. As an emerging biomaterial for bone defect treatment, graphene oxide (GO) in particular has gained substantial attention from researchers due to its potential applications and prospects. In other words, GO scaffolds have demonstrated remarkable potential for bone defect treatment. Furthermore, GO-loaded biomaterials can promote osteoblast adhesion, proliferation, and differentiation while stimulating bone matrix deposition and formation. Given their favourable biocompatibility and osteoinductive capabilities, these materials offer a novel therapeutic avenue for bone tissue regeneration and repair. This comprehensive review systematically outlines GO scaffolds’ diverse roles and potential applications in bone defect treatment.

Cite this article: Bone Joint Res 2024;13(12):725–740.


Bone & Joint 360
Vol. 4, Issue 4 | Pages 30 - 31
1 Aug 2015

The August 2015 Oncology Roundup. 360 . looks at: Glasgow prognostic score in soft-tissue sarcoma; Denosumab in giant cell tumour; Timing, complications and radiotherapy; Pigmented villonodular synovitis and arthroscopy; PATHFx: estimating survival in pathological cancer; Prosthetic lengthening of short stumps; Chondrosarcoma and pathological fracture


Bone & Joint 360
Vol. 13, Issue 1 | Pages 35 - 38
1 Feb 2024

The February 2024 Oncology Roundup360 looks at: Does primary tumour resection improve survival for patients with sarcomas of the pelvis with metastasis at diagnosis?; Proximal femur replacements for an oncologic indication offer a durable endoprosthetic reconstruction option: a 40-year experience; The importance of awaiting biopsy results in solitary pathological proximal femoral fractures: do we need to biopsy solitary pathological fractures?; Effect of radiotherapy on local recurrence, distant metastasis, and overall survival in 1,200 extremity soft-tissue sarcoma patients; What to choose in bone tumour resections? Patient-specific instrumentation versus surgical navigation; Optimal timing of re-excision in synovial sarcoma patients: immediate intervention versus waiting for local recurrence; Survival differences of patients with resected extraskeletal osteosarcoma receiving two different (neo) adjuvant chemotherapy regimens; Solitary versus multiple bone metastases in the appendicular skeleton: should the surgical treatment be different?.


Bone & Joint Open
Vol. 4, Issue 10 | Pages 766 - 775
13 Oct 2023
Xiang L Singh M McNicoll L Moppett IK

Aims

To identify factors influencing clinicians’ decisions to undertake a nonoperative hip fracture management approach among older people, and to determine whether there is global heterogeneity regarding these factors between clinicians from high-income countries (HIC) and low- and middle-income countries (LMIC).

Methods

A SurveyMonkey questionnaire was electronically distributed to clinicians around the world through the Fragility Fracture Network (FFN)’s Perioperative Special Interest Group and clinicians’ personal networks between 24 May and 25 July 2021. Analyses were performed using Excel and STATA v16.0. Between-group differences were determined using independent-samples t-tests and chi-squared tests.


Bone & Joint Research
Vol. 12, Issue 5 | Pages 311 - 312
5 May 2023
Xu C Liu Y

Cite this article: Bone Joint Res 2023;12(5):311–312.


Bone & Joint 360
Vol. 2, Issue 6 | Pages 2 - 8
1 Dec 2013
Jones R Wood D

This article provides an overview of the role of genomics in sarcomas and describes how new methods of analysis and comparative screening have provided the potential to progress understanding and treatment of sarcoma. This article reviews genomic techniques, the evolution of the use of genomics in cancer, the current state of genomic analysis, and also provides an overview of the medical, social and economic implications of recent genomic advances


Bone & Joint Open
Vol. 4, Issue 6 | Pages 442 - 446
12 Jun 2023
Toda Y Iwata S Kobayashi E Ogura K Osaki S Fukushima S Mawatari M Kawai A

Aims

The risk of postoperative complications after resection of soft-tissue sarcoma in the medial thigh is higher than in other locations. This study investigated whether a vessel sealing system (VSS) could help reduce the risk of postoperative complications after wide resection of soft-tissue sarcoma in the medial thigh.

Methods

Of 285 patients who underwent wide resection for soft-tissue sarcoma between 2014 and 2021 at our institution, 78 patients with tumours in the medial thigh were extracted from our database. Information on clinicopathological characteristics, preoperative treatment, surgical treatment (use of VSS, blood loss volume, operating time), and postoperative course (complications, postoperative haemoglobin changes, total drainage volume, and drainage and hospitalization durations) were obtained from medical records. We statistically compared clinical outcomes between patients whose surgery did or did not use VSS (VSS and non-VSS groups, respectively).


The Bone & Joint Journal
Vol. 98-B, Issue 2 | Pages 271 - 277
1 Feb 2016
Sørensen MS Gerds TA Hindsø K Petersen MM

Aims. The purpose of this study was to develop a prognostic model for predicting survival of patients undergoing surgery owing to metastatic bone disease (MBD) in the appendicular skeleton. Methods. We included a historical cohort of 130 consecutive patients (mean age 64 years, 30 to 85; 76 females/54 males) who underwent joint arthroplasty surgery (140 procedures) owing to MBD in the appendicular skeleton during the period between January 2003 and December 2008. Primary cancer, pre-operative haemoglobin, fracture versus impending fracture, Karnofsky score, visceral metastases, multiple bony metastases and American Society of Anaesthesiologist’s score were included into a series of logistic regression models. The outcome was the survival status at three, six and 12 months respectively. Results were internally validated based on 1000 cross-validations and reported as time-dependent area under the receiver-operating characteristic curves (AUC) for predictions of outcome. . Results. The predictive scores obtained showed AUC values of 79.1% (95% confidence intervals (CI) 65.6 to 89.6), 80.9% (95% CI 70.3 to 90.84) and 85.1% (95% CI 73.5 to 93.9) at three, six and 12 months. . Discussion. In conclusion, we have presented and internally validated a model for predicting survival after surgery owing to MBD in the appendicular skeleton. The model is the first, to our knowledge, built solely on material from patients who only had surgery in the appendicular skeleton. Take home message: Applying this prognostic model will help determine whether the patients’ anticipated survival makes it reasonable to subject them to extensive reconstructive surgery for which there may be an extended period of rehabilitation. Cite this article: Bone Joint J 2016;98-B:271–7


The Bone & Joint Journal
Vol. 98-B, Issue 2 | Pages 266 - 270
1 Feb 2016
Stevenson JD McNair M Cribb GL Cool WP

Aims. Surgical intervention in patients with bone metastases from breast cancer is dependent on the estimated survival of the patient. The purpose of this paper was to identify factors that would predict survival so that specific decisions could be made in terms of surgical (or non-surgical) management. . Methods. The records of 113 consecutive patients (112 women) with metastatic breast cancer were analysed for clinical, radiological, serological and surgical outcomes. Their median age was 61 years (interquartile range 29 to 90) and the median duration of follow-up was 1.6 years (standard deviation (. sd. ) 1.9, 95% confidence interval (CI) 0 to 5.9). The cumulative one- and five-year rates of survival were 68% and 16% (95% Cl 60 to 77 and 95% CI 10 to 26, respectively). . Results. Linear discriminant analysis identified a ‘quadruple A’ predictor of survival by reclassifying the sum of the albumin, adjusted calcium, alkaline phosphatase and age covariates each multiplied by a determined factor. The accuracy of this ‘quadruple A’ predictor was 90% with a sensitivity of 100% and a specificity of 88%. A receiver operating characteristic (ROC) curve revealed an area under the curve of 79%. Survival analysis for this ‘quadruple A’ predictor (<  = one or > one year survival) was statistically significant using the log rank test (p = 0.0004) and Cox proportional hazard (p = 0.001). Multivariate analysis showed the 'quadruple A' predictor to be the only independent predictor of survival (p = 0.01). . Discussion. The 'quadruple A' predictor, together with other positive predictors of survival, can be used by oncologists, orthopaedic and breast surgeons to estimate survival and therefore guide management. Cite this article: Bone Joint J 2016;98-B:266–70


Bone & Joint Open
Vol. 4, Issue 5 | Pages 338 - 356
10 May 2023
Belt M Robben B Smolders JMH Schreurs BW Hannink G Smulders K

Aims

To map literature on prognostic factors related to outcomes of revision total knee arthroplasty (rTKA), to identify extensively studied factors and to guide future research into what domains need further exploration.

Methods

We performed a systematic literature search in MEDLINE, Embase, and Web of Science. The search string included multiple synonyms of the following keywords: "revision TKA", "outcome" and "prognostic factor". We searched for studies assessing the association between at least one prognostic factor and at least one outcome measure after rTKA surgery. Data on sample size, study design, prognostic factors, outcomes, and the direction of the association was extracted and included in an evidence map.


The Bone & Joint Journal
Vol. 105-B, Issue 5 | Pages 551 - 558
1 May 2023
Wang H Ji T Qu H Yan T Li D Yang R Tang X Guo W

Aims

The aim of this study was to determine the rate of indocyanine green (ICG) staining of bone and soft-tissue tumours, as well as the stability and accuracy of ICG fluorescence imaging in detecting tumour residuals during surgery for bone and soft-tissue tumours.

Methods

ICG fluorescence imaging was performed during surgery in 34 patients with bone and soft-tissue tumours. ICG was administered intravenously at a dose of 2 mg/kg over a period of 60 minutes on the day prior to surgery. The tumour stain rate and signal-to-background ratio of each tumour were post hoc analyzed. After tumour resection, the tumour bed was scanned to locate sites with fluorescence residuals, which were subsequently inspected and biopsied.


Bone & Joint 360
Vol. 3, Issue 1 | Pages 32 - 34
1 Feb 2014

The February 2014 Oncology Roundup. 360 . looks at: suspicious lesions; limb salvage in pelvic sarcomas; does infection affect oncological survival?; cancer patient pathways; radiological arthritis with cement augmentation in GCT; and post-chemotherapy increase in tumour volume as a predictor of poor prognosis


The Bone & Joint Journal
Vol. 98-B, Issue 2 | Pages 160 - 165
1 Feb 2016
Farrier AJ C. Sanchez Franco L Shoaib A Gulati V Johnson N Uzoigwe CE Choudhury MZ

The ageing population and an increase in both the incidence and prevalence of cancer pose a healthcare challenge, some of which is borne by the orthopaedic community in the form of osteoporotic fractures and metastatic bone disease. In recent years there has been an increasing understanding of the pathways involved in bone metabolism relevant to osteoporosis and metastases in bone. Newer therapies may aid the management of these problems. One group of drugs, the antibody mediated anti-resorptive therapies (AMARTs) use antibodies to block bone resorption pathways. This review seeks to present a synopsis of the guidelines, pharmacology and potential pathophysiology of AMARTs and other new anti-resorptive drugs. . We evaluate the literature relating to AMARTs and new anti-resorptives with special attention on those approved for use in clinical practice. Denosumab, a monoclonal antibody against Receptor Activator for Nuclear Factor Kappa-B Ligand. It is the first AMART approved by the National Institute for Health and Clinical Excellence and the US Food and Drug Administration. Other novel anti-resorptives awaiting approval for clinical use include Odanacatib. Denosumab is indicated for the treatment of osteoporosis and prevention of the complications of bone metastases. Recent evidence suggests, however, that denosumab may have an adverse event profile similar to bisphosphonates, including atypical femoral fractures. It is, therefore, essential that orthopaedic surgeons are conversant with these medications and their safe usage. . Take home message: Denosumab has important orthopaedic indications and has been shown to significantly reduce patient morbidity in osteoporosis and metastatic bone disease. Cite this article: Bone Joint J 2016;98-B:160–5


Bone & Joint 360
Vol. 11, Issue 6 | Pages 40 - 41
1 Dec 2022

The December 2022 Oncology Roundup360 looks at: Is high-dose radiation therapy associated with early revision with a cemented endoprosthesis?; Neoadjuvant chemotherapy and endoprosthetic reconstruction for lower extremity sarcomas: does timing impact complication rates?; Late amputation after treatment for lower extremity sarcoma; Osteosarcoma prediagnosed as another tumour: a report from the Cooperative Osteosarcoma Study Group; The influence of site on the incidence and diagnosis of solitary central cartilage tumours of the femur: a 21st century perspective.


Bone & Joint Research
Vol. 7, Issue 2 | Pages 179 - 186
1 Feb 2018
Wu T Zhang J Wang B Sun Y Liu Y Li G

Objectives. As one of the heat-stable enterotoxins, Staphylococcal enterotoxin C2 (SEC2) is synthesized by Staphylococcus aureus, which has been proved to inhibit the growth of tumour cells, and is used as an antitumour agent in cancer immunotherapy. Although SEC2 has been reported to promote osteogenic differentiation of human mesenchymal stem cells (MSCs), the in vivo function of SCE2 in animal model remains elusive. The aim of this study was to further elucidate the in vivo effect of SCE2 on fracture healing. Materials and Methods. Rat MSCs were used to test the effects of SEC2 on their proliferation and osteogenic differentiation potentials. A rat femoral fracture model was used to examine the effect of local administration of SEC2 on fracture healing using radiographic analyses, micro-CT analyses, biomechanical testing, and histological analyses. Results. While SEC2 was found to have no effect on rat MSCs proliferation, it promoted the osteoblast differentiation of rat MSCs. In the rat femoral fracture model, the local administration of SEC2 accelerated fracture healing by increasing fracture callus volumes, bone volume over total volume (BV/TV), and biomechanical recovery. The SEC2 treatment group has superior histological appearance compared with the control group. Conclusion. These data suggest that local administration of SEC2 may be a novel therapeutic approach to enhancing bone repair such as fracture healing. Cite this article: T. Wu, J. Zhang, B. Wang, Y. Sun, Y. Liu, G. Li. Staphylococcal enterotoxin C2 promotes osteogenesis of mesenchymal stem cells and accelerates fracture healing. Bone Joint Res 2018;7:179–186. DOI: 10.1302/2046-3758.72.BJR-2017-0229.R1


Bone & Joint Research
Vol. 13, Issue 8 | Pages 411 - 426
28 Aug 2024
Liu D Wang K Wang J Cao F Tao L

Aims

This study explored the shared genetic traits and molecular interactions between postmenopausal osteoporosis (POMP) and sarcopenia, both of which substantially degrade elderly health and quality of life. We hypothesized that these motor system diseases overlap in pathophysiology and regulatory mechanisms.

Methods

We analyzed microarray data from the Gene Expression Omnibus (GEO) database using weighted gene co-expression network analysis (WGCNA), machine learning, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to identify common genetic factors between POMP and sarcopenia. Further validation was done via differential gene expression in a new cohort. Single-cell analysis identified high expression cell subsets, with mononuclear macrophages in osteoporosis and muscle stem cells in sarcopenia, among others. A competitive endogenous RNA network suggested regulatory elements for these genes.


Bone & Joint 360
Vol. 13, Issue 4 | Pages 40 - 42
2 Aug 2024

The August 2024 Research Roundup360 looks at: Effect of vitamin D deficiency on periprosthetic joint infection and complications after primary total joint replacement; Postoperative angiotensin receptor blocker use associated with decreased rates of manipulation under anaesthesia in patients undergoing total knee arthroplasty; Central sensitization: the missing link between psychological distress and poor outcome following primary total knee arthroplasty; Thromboprophylaxis for the trauma and orthopaedic surgeon; Life expectancy after treatment of metastatic bone disease: an international trend analysis.